chr5-156585183-C-T

Variant names:

• chr5-156585183-C-T
• rs10071215
• NM_000337.6:c.295-4048C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000337.6(SGCD):​c.295-4048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,180 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.031 (175 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 1 publications found

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000337.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	NM_000337.6	MANE Select	c.295-4048C>T		intron	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.292-4048C>T		intron	N/A	NP_001121681.1
	SGCD	NM_172244.3		c.295-4048C>T		intron	N/A	NP_758447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.295-4048C>T		intron	N/A	ENSP00000338343.4
	SGCD	ENST00000435422.7	TSL:1	c.292-4048C>T		intron	N/A	ENSP00000403003.2
	SGCD	ENST00000959784.1		c.346-4048C>T		intron	N/A	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4751 AN: 152062 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0313 AC: 4767 AN: 152180 Hom.: 175 Cov.: 32 AF XY: 0.0311 AC XY: 2316 AN XY: 74410

African (AFR) AF: 0.0790 AC: 3281 AN: 41514

American (AMR) AF: 0.0217 AC: 331 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.0510 AC: 264 AN: 5174

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4820

European-Finnish (FIN) AF: 0.00585 AC: 62 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00923 AC: 628 AN: 68004

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.00663 Hom.: 5

Bravo AF: 0.0344

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.80
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10071215; hg19: chr5-156012193;